View source for 6b9p


==Structure of GH 38 Jack Bean alpha-mannosidase in complex with a 36-valent iminosugar cluster inhibitor==
<StructureSection load='6b9p' size='340' side='right'caption='[[6b9p]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6b9p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Canavalia_ensiformis Canavalia ensiformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B9P FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.996&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=D0J:(2R,3R,4R,5S)-2-(hydroxymethyl)-1-{9-[4-(methoxymethyl)-1H-1,2,3-triazol-1-yl]nonyl}piperidine-3,4,5-triol'>D0J</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6b9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b9p OCA], [https://pdbe.org/6b9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b9p RCSB], [https://www.ebi.ac.uk/pdbsum/6b9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b9p ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MANA_CANEN MANA_CANEN] Liberates mannose from p-nitrophenyl-alpha-D-mannoside (PubMed:1156387, PubMed:12325362, PubMed:4973951). Liberates mannose from further alpha-D-mannosides including methyl-, benzyl-alpha-D-mannoside, 1-6-linked di-, tri- and tetrasaccharides of alpha-D-mannose and mannosyl-rhamnose (PubMed:12325362). Liberates mannose from various glycoproteins like ovalbumin and ovomucoid (PubMed:12325362, PubMed:5145). Does not hydrolyze beta-D-mannosides (PubMed:12325362). Has glycosyltransferase activity, forming disaccharides from mannose and lyxose but not from glucose, galactose, ribose, xylose or arabinose (PubMed:12325362).<ref>PMID:1156387</ref> <ref>PMID:12325362</ref> <ref>PMID:4973951</ref> <ref>PMID:5145</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Multivalent design of glycosidase inhibitors is a promising strategy for the treatment of diseases involving enzymatic hydrolysis of glycosidic bonds in carbohydrates. An essential prerequisite for successful applications is the atomic-level understanding of how outstanding binding enhancement occurs with multivalent inhibitors. Herein we report the first high-resolution crystal structures of the Jack bean alpha-mannosidase (JBalpha-man) in apo and inhibited states. The three-dimensional structure of JBalpha-man in complex with the multimeric cyclopeptoid-based inhibitor displaying the largest binding enhancements reported so far provides decisive insight into the molecular mechanisms underlying multivalent effects in glycosidase inhibition.

Structural Basis of Outstanding Multivalent Effects in Jack Bean alpha-Mannosidase Inhibition.,Howard E, Cousido-Siah A, Lepage ML, Schneider JP, Bodlenner A, Mitschler A, Meli A, Izzo I, Alvarez HA, Podjarny A, Compain P Angew Chem Int Ed Engl. 2018 Jul 2;57(27):8002-8006. doi: 10.1002/anie.201801202., Epub 2018 Jun 6. PMID:29722924<ref>PMID:29722924</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6b9p" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Canavalia ensiformis]]
[[Category: Large Structures]]
[[Category: Bodlenner A]]
[[Category: Compain P]]
[[Category: Cousido-Siah A]]
[[Category: De Riccardis F]]
[[Category: Howard E]]
[[Category: Izzo I]]
[[Category: Lepage M]]
[[Category: Meli A]]
[[Category: Mitschler A]]
[[Category: Podjarny A]]